Human Gene PSEN2 (uc009xep.1)
  Description: Homo sapiens presenilin 2 (Alzheimer disease 4) (PSEN2), transcript variant 2, mRNA.
RefSeq Summary (NM_012486): Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr1:227,058,273-227,083,804 Size: 25,532 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr1:227,069,609-227,083,280 Size: 13,672 Coding Exon Count: 10 

Page IndexSequence and LinksPrimersGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
mRNA DescriptionsPathwaysOther NamesGeneReviewsModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:227,058,273-227,083,804)mRNA (may differ from genome)Protein (447 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMalacardsMGI
OMIMPubMedReactomeTreefamUniProtKBWikipedia
BioGrid CRISPR DB

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PSEN2
CDC HuGE Published Literature: PSEN2
Positive Disease Associations: Alzheimer's Disease , Echocardiography
Related Studies:
  1. Alzheimer's Disease
    Ezquerra M 2003, A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease., Archives of neurology. 2003 Aug;60(8):1149-51. [PubMed 12925374]
    We have found a novel mutation in the PSEN2 gene in a family with early-onset Alzheimer disease. The variation in the age at onset confirms that PSEN2 mutations are associated with variable clinical expression.
  2. Alzheimer's Disease
    Di Natale M et al. 2003, Absence of association between Alzheimer disease and the regulatory region polymorphism of the PS2 gene in an Italian population., Neuroscience letters. 2003 Jun;343(3):210-2. [PubMed 12770698]
    The current study does not support the notion that the polymorphism in the PS2 gene constitutes a risk factor for either late-onset or early-onset AD, which means that other genetic factors play a role in the development of AD in the Italian population.
  3. Echocardiography
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PSEN2
Diseases sorted by gene-association score: alzheimer disease-4* (1351), cardiomyopathy, dilated, 1v* (529), early-onset, autosomal dominant alzheimer disease* (368), early-onset familial alzheimer disease* (219), familial isolated dilated cardiomyopathy* (143), psen2-related dilated cardiomyopathy* (100), alzheimer disease (37), pharyngoconjunctival fever (16), alzheimer disease, type 3 (12), acute conjunctivitis (12), acute hemorrhagic conjunctivitis (11), dementia (11), alzheimer disease-2 (9), visual agnosia (8), dementia, frontotemporal (6), shipyard eye (5), punctate epithelial keratoconjunctivitis (5), inclusion conjunctivitis (5), conjunctival disease (5), cardiomyopathy (3), nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C006780 bisphenol A
  • C006253 pirinixic acid
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C495626 14-deoxy-11,12-didehydroandrographolide
  • C023514 2,6-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • D000082 Acetaminophen
  • D016604 Aflatoxin B1
  • D000452 Aldrin
  • D000643 Ammonium Chloride
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.30 RPKM in Pancreas
Total median expression: 316.94 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -160.00427-0.375 Picture PostScript Text
3' UTR -168.80524-0.322 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  Pfam Domains:
PF01080 - Presenilin

ModBase Predicted Comparative 3D Structure on P49810-3
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Descriptions from all associated GenBank mRNAs
  AK301143 - Homo sapiens cDNA FLJ51336 complete cds, highly similar to Presenilin-2 (EC 3.4.23.-).
AK292299 - Homo sapiens cDNA FLJ77434 complete cds, highly similar to Homo sapiens presenilin 2 (Alzheimer disease 4) (PSEN2), transcript variant 2, mRNA.
L43964 - Homo sapiens (clone F-T03796) STM-2 mRNA, complete cds.
L44577 - Homo sapiens S182 protein homologue (E5-1) mRNA, complete cds.
BC006365 - Homo sapiens presenilin 2 (Alzheimer disease 4), mRNA (cDNA clone MGC:12801 IMAGE:4131408), complete cds.
JD062373 - Sequence 43397 from Patent EP1572962.
JD530053 - Sequence 511077 from Patent EP1572962.
JD114939 - Sequence 95963 from Patent EP1572962.
JD339275 - Sequence 320299 from Patent EP1572962.
JD164571 - Sequence 145595 from Patent EP1572962.
JD216067 - Sequence 197091 from Patent EP1572962.
U34349 - Human seven trans-membrane domain protein (AD3LP/AD5) mRNA, complete cds.
JD328258 - Sequence 309282 from Patent EP1572962.
AF416718 - Homo sapiens presenilin 2 transcript variant 2 mRNA, partial cds.
CU675365 - Synthetic construct Homo sapiens gateway clone IMAGE:100019452 5' read PSEN2 mRNA.
AB527264 - Synthetic construct DNA, clone: pF1KB5356, Homo sapiens PSEN2 gene for presenilin 2, without stop codon, in Flexi system.
BT006984 - Homo sapiens presenilin 2 (Alzheimer disease 4) mRNA, complete cds.
DQ890646 - Synthetic construct clone IMAGE:100003276; FLH164751.01X; RZPDo839B07158D presenilin 2 (Alzheimer disease 4) (PSEN2) gene, encodes complete protein.
DQ893826 - Synthetic construct Homo sapiens clone IMAGE:100008286; FLH164747.01L; RZPDo839B07157D presenilin 2 (Alzheimer disease 4) (PSEN2) gene, encodes complete protein.
KJ897395 - Synthetic construct Homo sapiens clone ccsbBroadEn_06789 PSEN2 gene, encodes complete protein.
KR710056 - Synthetic construct Homo sapiens clone CCSBHm_00009256 PSEN2 (PSEN2) mRNA, encodes complete protein.
KR710057 - Synthetic construct Homo sapiens clone CCSBHm_00009262 PSEN2 (PSEN2) mRNA, encodes complete protein.
KR710058 - Synthetic construct Homo sapiens clone CCSBHm_00009266 PSEN2 (PSEN2) mRNA, encodes complete protein.
KR710059 - Synthetic construct Homo sapiens clone CCSBHm_00009270 PSEN2 (PSEN2) mRNA, encodes complete protein.
JD223695 - Sequence 204719 from Patent EP1572962.
JD082383 - Sequence 63407 from Patent EP1572962.
JD233746 - Sequence 214770 from Patent EP1572962.
JD057541 - Sequence 38565 from Patent EP1572962.
JD317839 - Sequence 298863 from Patent EP1572962.
JD317323 - Sequence 298347 from Patent EP1572962.
JD370707 - Sequence 351731 from Patent EP1572962.
JD210509 - Sequence 191533 from Patent EP1572962.
JD121192 - Sequence 102216 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04330 - Notch signaling pathway
hsa05010 - Alzheimer's disease

BioCarta from NCI Cancer Genome Anatomy Project
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF

Reactome (by CSHL, EBI, and GO)

Protein P49810 (Reactome details) participates in the following event(s):

R-HSA-157353 NEXT1 is cleaved to produce NICD1
R-HSA-157640 NEXT2 is cleaved to produce NICD2
R-HSA-157648 NEXT4 is cleaved to produce NICD4
R-NUL-2197556 Gamma-secretase complex cleaves mNEXT2
R-HSA-2220988 NEXT1 PEST domain mutants are cleaved to produce NICD1 PEST domain mutants
R-HSA-9013361 NEXT3 is cleaved to produce NICD3
R-HSA-193682 gamma-secretase cleaves the p75NTR transmembrane domain
R-HSA-1251997 Cleavage of ERBB4m80 by gamma-scretase complex
R-HSA-205112 gamma-secretase cleaves p75NTR, releasing NRIF and TRAF6
R-HSA-157212 A third proteolytic cleavage releases NICD
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-1980150 Signaling by NOTCH4
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9017802 Noncanonical activation of NOTCH3
R-HSA-193692 Regulated proteolysis of p75NTR
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-205043 NRIF signals cell death from the nucleus
R-HSA-1980143 Signaling by NOTCH1
R-HSA-1980145 Signaling by NOTCH2
R-HSA-157118 Signaling by NOTCH
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-9012852 Signaling by NOTCH3
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-1236394 Signaling by ERBB4
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-162582 Signal Transduction
R-HSA-2644603 Signaling by NOTCH1 in Cancer
R-HSA-73887 Death Receptor Signalling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-422475 Axon guidance
R-HSA-5663202 Diseases of signal transduction
R-HSA-1266738 Developmental Biology
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: AD4, NM_012486, NP_036618, P49810-3, PS2, PSNL2, STM2
UCSC ID: uc009xep.1
RefSeq Accession: NM_012486
Protein: P49810-3, splice isoform of P49810 CCDS: CCDS1556.1, CCDS44324.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PSEN2:
alzheimer (Alzheimer Disease Overview)
dcm-ov (Dilated Cardiomyopathy Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_012486.2
exon count: 13CDS single in 3' UTR: no RNA size: 2299
ORF size: 1344CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2868.50frame shift in genome: no % Coverage: 99.83
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.